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https://www.readbyqxmd.com/read/28734368/exploring-pralidoxime-chloride-as-a-universal-electrochemical-probe-for-organophosphorus-pesticides-detection
#1
Qiqi Zheng, Yuan Chen, Kai Fan, Jian Wu, Yibin Ying
An electrochemical method based on non-enzymatic inhibition for the determination of organophosphorus pesticide (OPPs) using pralidoxime chloride (PAM-Cl) as a universal electrochemical probe was reported. Cyclic voltammetry was performed to characterize the redox properties of pralidoxime and OPPs. Differential pulse voltammetry (DPV) was carried out to analyze the influence of anion (chloride and iodide ions), to optimize the pH of testing condition, and to explore the relationship between pralidoxime and OPPs...
August 22, 2017: Analytica Chimica Acta
https://www.readbyqxmd.com/read/28722512/in-silico-and-in-vitro-evaluation-of-two-novel-oximes-k378-and-k727-in-comparison-to-k27-and-pralidoxime-against-paraoxon-ethyl-intoxication
#2
Maria Chaudhry, Muhammad Qaiser Fatmi, Kamil Musilek, Alamdar Hussain, Kamil Kuca, Georg Petroianu, Huba Kalasz, Syed Muhammad Nurulain
Organophosphate (OP) poisoning is a major global health issue; while compounds from this group have been used intensively over the last century, an effective antidote is still lacking. Oxime-type AChE reactivators are used to reactivate the OP inhibited AChE. Pralidoxime is the only US Food and Drug Administration, (FDA) approved oxime for therapeutic use but its efficacy has been disappointing. Two novel oximes (K378 and K727) were investigated in silico and in vitro and compared with an experimental oxime (kamiloxime; K-27) and pralidoxime...
July 19, 2017: Toxicology Mechanisms and Methods
https://www.readbyqxmd.com/read/28648599/2-3-butandione-2-monoxime-inhibits-skeletal-myosin-ii-by-accelerating-atp-cleavage
#3
Hideyuki Komatsu, Yuji Koseki, Takeshi Kanno, Shunsuke Aoki, Takao Kodama
2,3-Butandione 2-monoxime (BDM) is a widely used myosin inhibitor with an unclear mode of action. In this report, we investigated the mechanism of BDM oxime group nucleophilic reactivity on the phosphoester bond of ATP. BDM increased the ATPase activity of skeletal myosin subfragment 1 (S1) under conditions in which ATP cleavage is the rate-limiting step (K(+), EDTA-ATPase activity of native S1 and Mg(2+)-ATPase activity of trinitrophenylated S1 and partially unfolded S1). Furthermore, the effect of BDM on the S1-bound adenosine 5'-(β,γ-imido) triphosphate (AMPPNP) (31)P NMR spectrum suggests that BDM changes the microenvironment around the phosphorus atoms of myosin-bound nucleotide...
August 26, 2017: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/28644688/intraosseous-administration-of-antidotes-a-systematic-review
#4
Audrée Elliott, Pierre-André Dubé, Amélie Cossette-Côté, Laura Patakfalvi, Eric Villeneuve, Martin Morris, Sophie Gosselin
CONTEXT: Intraosseous (IO) access is an established route of administration in resuscitation situations. Patients with serious poisoning presenting to the emergency department may require urgent antidote therapy. However, intravenous (IV) access is not always readily available. OBJECTIVE: This study reviews the current evidence for IO administration of antidotes that could be used in poisoning. The primary outcome was mortality as a surrogate of efficacy. Secondary outcomes included hemodynamic variables, electrocardiographic variables, neurological status, pharmacokinetics outcomes, and adverse effects as defined by each article...
June 23, 2017: Clinical Toxicology
https://www.readbyqxmd.com/read/28504886/nanoparticle-delivered-2-pam-for-rat-brain-protection-against-paraoxon-central-toxicity
#5
Tatiana N Pashirova, Irina V Zueva, Konstantin A Petrov, Vasily M Babaev, Svetlana S Lukashenko, Ildar Kh Rizvanov, Eliana B Souto, Evgeny E Nikolsky, Lucia Ya Zakharova, Patrick Masson, Oleg G Sinyashin
Solid lipid nanoparticles (SLNs) are among the most promising nanocarriers to target the blood-brain barrier (BBB) for drug delivery to the central nervous system (CNS). Encapsulation of the acetylcholinesterase reactivator, pralidoxime chloride (2-PAM), in SLNs appears to be a suitable strategy for protection against poisoning by organophosphorus agents (OPs) and postexposure treatment. 2-PAM-loaded SLNs were developed for brain targeting and delivery via intravenous (iv) administration. 2-PAM-SLNs displayed a high 2-PAM encapsulation efficiency (∼90%) and loading capacity (maximum 30...
May 15, 2017: ACS Applied Materials & Interfaces
https://www.readbyqxmd.com/read/28499841/effect-of-administration-method-animal-weight-and-age-on-the-intranasal-delivery-of-drugs-to-the-brain
#6
Jishnu K S Krishnan, Peethambaran Arun, Bhadra Chembukave, Abhilash P Appu, Nivetha Vijayakumar, John R Moffett, Narayanan Puthillathu, Aryan M A Namboodiri
BACKGROUND: The intranasal route of administration has proven to be an effective method for bypassing the blood brain barrier and avoiding first pass hepatic metabolism when targeting drugs to the brain. Most small molecules gain rapid access to CNS parenchyma when administered intranasally. However, bioavailability is affected by various factors ranging from the molecular weight of the drug to the mode of intranasal delivery. COMPARISON WITH EXISTING METHODS: We examined the effects of animal posture, intranasal application method and animal weight and age on the delivery of radiolabeled pralidoxime ((3)H-2-PAM) to the brain of rats...
July 15, 2017: Journal of Neuroscience Methods
https://www.readbyqxmd.com/read/28478772/are-dutch-hospitals-prepared-for-chemical-biological-or-radionuclear-incidents-a-survey-study
#7
Luc J M Mortelmans, Menno I Gaakeer, Greet Dieltiens, Kurt Anseeuw, Marc B Sabbe
Introduction Being one of Europe's most densely populated countries, and having multiple nuclear installations, a heavy petrochemical industry, and terrorist targets, the Netherlands is at-risk for chemical, biological, or radionuclear (CBRN) incidents. Recent world and continental events show that this threat is real and that authorities may be underprepared. Hypothesis The hypothesis of this study is that Dutch hospitals are underprepared to deal with these incidents. METHODS: A descriptive, cross-sectional study was performed...
May 8, 2017: Prehospital and Disaster Medicine
https://www.readbyqxmd.com/read/28464765/functional-chemical-groups-that-may-likely-become-source-for-synthesis-of-novel-central-nervous-system-cns-acting-drugs
#8
Saganuwan Alhaji Saganuwan
Central nervous system (CNS) disorders are on increase perhaps due to genetic, enviromental, social and dietetic factors. Unfortunately, a large number of CNS drugs have adverse effects such as addiction, tolerance, psychological and physical dependence. In view of this, literature search was carried out with a view to identifying functional chemical groups that may serve as lead molecule for synthesis of compounds that may have CNS activity. The search revealed that heterocycles that have heteroatoms such as nitrogen (N), sulphur (S) and oxygen (O) form the largest class of organic compounds...
May 2, 2017: Central Nervous System Agents in Medicinal Chemistry
https://www.readbyqxmd.com/read/28404526/stereospecific-cholinesterase-inhibition-by-o-s-diethylphenylphosphonothioate
#9
Ahmed Mohammed, Jennifer Sneathen, Sara Glazier Frojen, Louis Kuo, Cynthia M Dupureur
The inhibition kinetics and stereospecificity of the chiral nerve agent derivative O,S-diethylphenylphosphonothioate (DEPP) were examined for two forms of acetylcholinesterase (human and eel) and equine butyrylcholinesterase. Both S- and R-DEPP are poor inhibitors of eel AChE (IC50 150μM), consistent with a large, nondiscriminatory binding interaction in the active site of this enzyme. However, S-DEPP is active against human and equine AChE with low μM IC50s. DEPP stereospecificities (S/R) toward these enzymes are moderate (20) relative to other cholinesterase-organophosphate (OP) systems...
June 15, 2017: Bioorganic & Medicinal Chemistry
https://www.readbyqxmd.com/read/28403672/toxic-megacolon-as-a-rare-complication-following-atropine-therapy-due-to-organophosphate-poisoning-a-case-report
#10
Babak Mostafazadeh, Esmaeil Farzaneh, Maryam Paeezi, Farahnaz Nikkhah
The main therapeutic basis for a case of organophosphate poisoning is a combination therapy which includes atropine as an anticholinergic drug and pralidoxime. If the poisoning is severe, a high dose of this combination of medicines may be needed, but this may cause serious side effects: paralytic ileus or even megacolon; however, these gastrointestinal events are very rare. Here, we report a case of organophosphate poisoning where atropine therapy was given and led to drug-associated toxic megacolon.
January 1, 2017: Medico-legal Journal
https://www.readbyqxmd.com/read/28329845/editor-s-highlight-spatiotemporal-progression-and-remission-of-lesions-in-the-rat-brain-following-acute-intoxication-with-diisopropylfluorophosphate
#11
Sílvia Sisó, Brad A Hobson, Danielle J Harvey, Donald A Bruun, Douglas J Rowland, Joel R Garbow, Pamela J Lein
Similar to organophosphate (OP) nerve agents, diisopropylfluorophosphate (DFP) rapidly and irreversibly inhibits acetylcholinesterase, leading to convulsions that can progress to status epilepticus (SE). However, in contrast to the OP nerve agents, the long-term consequences of DFP-induced SE are not well known. Thus, we characterized the spatiotemporal profile of neuropathology during the first 2 months following acute DFP intoxication. Adult, male Sprague Dawley rats administered pyridostigmine bromide (0...
June 1, 2017: Toxicological Sciences: An Official Journal of the Society of Toxicology
https://www.readbyqxmd.com/read/28329842/from-the-cover-magneticresonance-imaging-reveals-progressive-brain-injury-in-rats-acutely-intoxicated-with-diisopropylfluorophosphate
#12
Brad A Hobson, Sílvia Sisó, Douglas J Rowland, Danielle J Harvey, Donald A Bruun, Joel R Garbow, Pamela J Lein
Acute intoxication with organophosphates (OPs) can trigger seizures that progress to status epilepticus, and survivors often exhibit chronic neuropathology, cognitive impairment, affective disorders, and/or electroencephalographic abnormalities. Understanding how acute injury transitions to persistent neurological sequelae is critical to developing medical countermeasures for mitigating damage following OP-induced seizures. Here, we used in vivo magnetic resonance imaging (MRI) to monitor the spatiotemporal patterns of neuropathology for 1 month after acute intoxication with diisopropylfluorophosphate (DFP)...
June 1, 2017: Toxicological Sciences: An Official Journal of the Society of Toxicology
https://www.readbyqxmd.com/read/28328690/the-first-use-of-pralidoxime-in-a-child-with-rivastigmine-poisoning
#13
Eylem Ulaş Saz, Ali Yurtseven, Mehmet Arda Kilinç, Yusuf Sari, Hasan Ağin
The aim of this report is to describe the successful use of pralidoxime in a pediatric patient who accidentally ingested 12 mg of rivastigmine and presented to the emergency department with weakness, drowsiness, hyporeactivity to environmental stimuli, and full cholinergic syndrome. CASE: The patient presented to the emergency department 2 hours after a suspected ingestion of rivastigmine. He was sleepy but oriented and cooperative, hypotonic, and hyporeflexic and has a Glasgow Coma Scale score of 13 (E3M6V4)...
March 21, 2017: Pediatric Emergency Care
https://www.readbyqxmd.com/read/28296779/efficacy-of-fresh-packed-red-blood-transfusion-in-organophosphate-poisoning
#14
RANDOMIZED CONTROLLED TRIAL
Hang-Xing Bao, Pei-Jian Tong, Cai-Xia Li, Jing Du, Bing-Yu Chen, Zhi-Hui Huang, Ying Wang
The mortality rate caused by organophosphate (OP) poisoning is still high, even the standard treatment such as atropine and oxime improves a lot. To search for alternative therapies, this study was aimed to investigate the effects of packed red blood cell (RBC) transfusion in acute OP poisoning, and compare the therapeutic effects of RBCs at different storage times.Patients diagnosed with OP poisoning were included in this prospective study. Fresh RBCs (packed RBCs stored less than 10 days) and longer-storage RBCs (stored more than 10 days but less than 35 days) were randomly transfused or not into OP poisoning patients...
March 2017: Medicine (Baltimore)
https://www.readbyqxmd.com/read/28106328/on-the-influence-of-the-protonation-states-of-active-site-residues-on-ache-reactivation-a-qm-mm-approach
#15
Thomas Driant, Florian Nachon, Cyril Ollivier, Pierre-Yves Renard, Etienne Derat
Acetylcholinesterase (AChE), an enzyme of the serine hydrolase superfamily, is a mediator of signal transmission at cholinergic synapses by catalyzing acetylcholine cleavage into acetate and choline. This enzyme is vulnerable to covalent inhibition by organophosphate compounds (like VX). Covalent inhibition of AChE does not revert spontaneously. Known reactivator compounds have limited action in restoring catalytic activity. QM/MM simulations of VX-inhibited AChE reactivation by pralidoxime (2-PAM), a classical reactivator, were performed...
January 19, 2017: Chembiochem: a European Journal of Chemical Biology
https://www.readbyqxmd.com/read/28078916/in-vivo-protection-studies-of-bis-quaternary-2-hydroxyimino-n-pyridin-3-yl-acetamide-derivatives-hnk-oximes-against-tabun-and-soman-poisoning-in-swiss-albino-mice
#16
P Kumar, D Swami, D P Nagar, K P Singh, J Acharya, H N Karade, R Yadav
The study reports antidotal efficacy of three HNK [ bis quaternary 2-(hydroxyimino)-N-(pyridin-3yl) acetamide derivatives] and pralidoxime (2-PAM), against soman and tabun poisoning in Swiss albino mice. Protection index (PI) was determined (treatment doses: HNK oximes, ×0.20 of their median lethal dose (LD50) and 2-PAM, 30 mg/kg, intramuscularly (im)) together with atropine (10 mg/kg, intraperitoneally). Probit log doses with difference of 0.301 log of LD50 of the nerve agents administered and inhibition of acetylcholinesterase (AChE) activity by 50% (IC50) was calculated at optimized time in brain and serum...
January 1, 2017: Human & Experimental Toxicology
https://www.readbyqxmd.com/read/28043418/the-effectiveness-of-patient-tailored-treatment-for-acute-organophosphate-poisoning
#17
RANDOMIZED CONTROLLED TRIAL
Chih-Chuan Lin, Dong-Zong Hung, Hsien-Yi Chen, Kuang-Hung Hsu
BACKGROUND: To determine a new pralidoxime (PAM) treatment guideline based on the severity of acute organophosphate intoxication patients, APACHE II score, and dynamic changes in serum butyrylcholinesterase (BuChE) activity. METHODS: This is a randomization trial. All patients received supportive care measurements and atropinization. Each enrolled patient was treated with 2 gm PAM intravenously as the loading dose. The control group was treated according to the WHO's recommended PAM regimen, and the experimental group was treated according to their APACHE II scores and dynamic changes in BuChE activity...
December 2016: Biomedical Journal
https://www.readbyqxmd.com/read/28043415/pralidoxime-and-pesticide-poisoning-a-question-of-severity
#18
EDITORIAL
Emma Louise Walton
In this issue of the Biomedical Journal, we highlight new data supporting the use of pralidoxime in the treatment of cases of organophosphate poisoning, which also suggest that WHO treatment guidelines should be updated. We also learn about a modified surgical technique to repair severe spinal injuries, as well as new insight into the structure of human adenovirus that could inform vaccine development.
December 2016: Biomedical Journal
https://www.readbyqxmd.com/read/27990564/planarian-cholinesterase-in-vitro-characterization-of-an-evolutionarily-ancient-enzyme-to-study-organophosphorus-pesticide-toxicity-and-reactivation
#19
Danielle Hagstrom, Hideto Hirokawa, Limin Zhang, Zoran Radic, Palmer Taylor, Eva-Maria S Collins
The freshwater planarian Dugesia japonica has recently emerged as an animal model for developmental neurotoxicology and found to be sensitive to organophosphorus (OP) pesticides. While previous activity staining of D. japonica, which possess a discrete cholinergic nervous system, has shown acylthiocholine catalysis, it is unknown whether this is accomplished through an acetylcholinesterase (AChE), butyrylcholinesterase (BChE), or a hybrid esterase and how OP exposure affects esterase activity. Here, we show that the majority of D...
December 18, 2016: Archives of Toxicology
https://www.readbyqxmd.com/read/27728587/pralidoxime-in-acute-organophosphate-poisoning-a-randomized-trial
#20
Bammigatti C, M Vinod Babu, T Kadhiravan, R P Swaminathan
No abstract text is available yet for this article.
January 2016: Journal of the Association of Physicians of India
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